miR-206 is required for changes in cell adhesion that drive muscle cell morphogenesis in Xenopus laevis

Abstract

MicroRNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression in multicellular organisms. Within the set of muscle-specific miRNAs, miR-206 expression is largely restricted to skeletal muscle and is found exclusively within the bony fish lineage. Although many studies have implicated miR-206 in muscle maintenance and disease, its role in skeletal muscle development remains largely unknown. Here, we examine the role of miR-206 during Xenopus laevis somitogenesis. In Xenopus laevis, miR-206 expression coincides with the onset of somitogenesis. We show that both knockdown and over-expression of miR-206 result in abnormal somite formation affecting muscle cell rotation, attachment, and elongation. In particular, our data suggests that miR-206 regulates changes in cell adhesion that affect the ability of newly formed somites to adhere to the notochord as well as to the intersomitic boundaries. Additionally, we show that β-dystroglycan and F-actin expression levels are significantly reduced, suggesting that knockdown of miR-206 levels affects cellular mechanics necessary for cell shape changes and attachments that are required for proper muscle formation.

miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

“…miR‐206 , miR‐1a‐1 , and miR‐1a‐2 are genes encoding mature miR‐206 and miR‐1a , muscle‐specific miRNAs (myomiRs), which not only have identical seed sequence, suggesting functional redundancy, but also are highly expressed in cardiac and skeletal muscle along with miR‐133a and miR‐133b . miR206 , miR‐1a‐1 , and miR‐1a‐2 were suggested to be a critical factor for skeletal muscle differentiation 7,8,19,20,36‐52 . However, there was no model where all three miRNA genes are knocked out to prove the essentiality of these myomiRs in myogenesis.…”

“…A conditional skeletal muscle‐specific knock‐out (KO) of Dicer in mice leads to global loss of miRNAs in developing skeletal muscle, resulting in widespread apoptosis and abnormal myofiber morphology 35 . Over the last 14 years miR‐206 , miR‐1a‐1 , and miR‐1a‐2 have been hypothesized to not only be very important for muscle differentiation, but also essential for this process 7,8,19‐21,36‐52 . miR‐206 , miR‐1a‐1 , and miR‐1a‐2 are members of the myomiR family and are expressed from bicistronic loci.…”

miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

“…A conditional skeletal muscle specific knockout of Dicer in mice leads to global loss of miRNAs in developing skeletal muscle, resulting in widespread apoptosis and abnormal myofiber morphology (O’Rourke et al, 2007). Over the last 14 years miR-206 , miR-1a-1 and miR-1a-2 have been hypothesized to not only be very important for muscle differentiation, but also essential for this process (Anderson et al, 2006; Chen et al, 2006; Chen et al, 2010; Dey et al, 2011; Gagan et al, 2012; Goljanek-Whysall et al, 2012; Heidersbach et al, 2013; Hirai et al, 2010; Kim et al, 2006; Koutsoulidou et al, 2011; Kwon et al, 2005; Mishima et al, 2009; Rao et al, 2006; Sokol and Ambros, 2005; Sweetman et al, 2008; Vergara et al, 2018; Wystub et al, 2013; Wüst et al, 2018; Yuasa et al, 2008; Zhao et al, 2007; Zhao et al, 2005). miR-206 , miR-1a-1 and miR-1a-2 are members of the myomir family and are expressed from bicistronic loci.…”

Functional Non-coding RNA During Embryonic Myogenesis and Postnatal Muscle Development and Disease

“…In Xenopus laevis, Vergara et al examined the expression of miR-206 accompanying somitogenesis. Both knockdown and overexpression of miR-206 resulted in abnormal somite formation (Vergara et al, 2018). Conversely, miR-133 knockdown impaired myotome formation and growth, and the evolutionarily conserved miR-133 family mediated Gli3 silencing was critical for embryonic myogenesis (Mok et al, 2018).…”